The University of Iowa Preclinical assessment Network (UIowa-SPAN) meets the goal of the NIH in maximizing efficiencies to develop and conduct rigorous pre-clinical comparative studies of neuroprotection in the context of stroke reperfusion. The current proposal builds on the rich tradition of the UIowa as a leader in preclinical and clinical NINDS-sponsored stroke research. This infrastructure brings together basic cerebrovascular scientists with vascular neurologists and clinical trialists to conduct rigorous animal trials of ischemia-reperfusion. We will capitalize on our experience using both male/female animals, co-morbidities (e.g. hyperlipidemia), combined with a rigorous methodology to minimize biases, including randomization, blinding, intention-to -treat analyses and independent outcome adjudications. Our proposal?s immediate goal is to advance the field of synergistic neuroprotective interventions by allowing uric acid (UA) progress from comparative animal experiments into phase II trials conducted in a future StrokeNet-developed research MT platform. Specifically, this proposal incorporates UA as one of the therapies to be tested through this preclinical assessment network. The free-radical (peroxynitrite) scavenger action of UA is crucial to minimize the brain reperfusion injury and lack of reflow that occurs after MT. UA has a strong record of efficacy in animals within STAIR/RIGOR guidelines, as well as an excellent record of safety and preliminary efficacy in patients treated with MT. Intravenous infusions of UA will be compared against the other candidate molecules in SPAN through blinded, randomized, adaptive experiments using the animals models and co-morbidities deemed necessary by the SPAN coordinating center. The proposal may have significant clinical implications by improving the outcomes of those Americans who suffer a stroke and require treatment with mechanical thrombectomy (MT).